Abstract WP267: Association Between Arterial Resistance and Subtypes of Cerebral Small Vessel Disease

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yongseok LEE ◽  
Ki-Woong Nam ◽  
Hyung-Min Kwon

Introduction: Increased arterial resistance is a potential pathophysiological mechanism in the pathogenesis of cerebral small vessel disease (cSVD). In this study, we aimed to investigate the association between puslatility index (PI) representing cerebral arterial resistance and subtypes of cSVD in patients with stroke due to small vessel occlusion (SVO). Hypothesis: Pattern of increased arterial resistance may be different between individual subtypes of cSVD. Methods: We included consecutive patients with SVO between 2010 and 2013. White matter hyperintensity (WMH) volume was rated using semi-automated quantitative methods. And the presence of old lacunar infarct (OLI), cerebral microbleed (CMB), or enlarged perivascular space (EPVS) was also evaluated. The relationship between PI, measured with transcranial Doppler sonography in each middle cerebral artery, and subtypes/burden of cSVD was analyzed in the relevant hemisphere. Results: A total of 206 patients with 412 hemispheres were included (mean age: 64 years, male: 68%). In multivariable analysis, PI was positively associated with the WMH volume [beta = 1.372, 95% confidence interval (CI) = 0.624 to 2.120, P < 0.001] after adjusting confounders. PI was also related to the presence of OLI (adjusted odds ratio = 11.37, 95% CI = 2.55-48.56, P = 0.001), however this relationship was not significant in CMB or EPVS. Regarding to the cSVD burden, PI increased according to the WMH tertiles ( P for trend < 0.001), and burden of OLI ( P for trend = 0.004) in a dose-response manner. Conclusion: Association of cerebral arterial resistance is different between subtypes of cSVD, which is suggestive of underlying pathophysiological difference. Simple measure of PI seems to be useful to estimate the arterial resistance and the burden of cSVD.

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Forrest Lowe ◽  
Souvik Sen ◽  
Hamdi S Adam ◽  
Ryan Demmer ◽  
Bruce A Wasserman ◽  
...  

Background: Prior studies have shown the association between periodontal disease, lacunar strokes and cognitive impairment. Using the Atherosclerosis Risk in Communities (ARIC) cohort study we investigated the relationship between periodontal disease (PD) and the development of MRI verified small vessel disease. Methods: Using the ARIC database data we extracted data for 1143 (mean age 77 years, 76% white, 24% African-American and 45% male) participants assessed for PD (N=800) versus periodontal health (N=343). These participants were assessed for small vessel disease on 3T MRI as measured by the log of white matter hyperintensity volume (WMHV). WMHV were derived from a semiautomated segmentation of FLAIR images. Student t-test was then used to evaluate the relationship between small vessel disease as the log of WMHV in subjects with PD or periodontal health. Based on WMHV the patients were grouped into quartiles and the association of PD with WMHV were tested using the group in periodontal health and lowest quartile of WMHV as the reference groups. Multinomial logistic regression was used to compute crude and adjusted odds ratio (OR) for the higher quartiles of WMHV compared to the reference quartile. Results: There was a significant increase in the presence of small vessel disease measured as log WMHV in the PD cohort as compared to periodontal health cohort with p= 0.023 on Independent Sample t-est. Based on WMHV the subjects were grouped into quartiles 0-6.41, >6.41-11.56, >11.56-21.36 and >21.36 cu mm3). PD was associated with only the highest quartile of WMHV on univariate (crude OR 1.77, 95% CI 1.23-2.56) and multivariable (adjusted OR 1.61, 95% CI 1.06-2.44) analyses. The later was adjusted for age, race, gender, hypertension, diabetes and smoking. Conclusion: Based on this prospective cohort there is data to suggest that PD may be associated with cerebral small vessel disease. Maintaining proper dental health may decrease future risk for the associated lacunar strokes and vascular cognitive impairment.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Dorothee Schoemaker ◽  
Yesica Zuluaga ◽  
Lina Velilla ◽  
Carolina Ospina ◽  
Francisco Lopera ◽  
...  

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease (cSVD) linked to NOTCH3 mutations and leading to the early onset of stroke and vascular cognitive impairment. Neuroimaging features of CADASIL include extensive white matter hyperintensity, lacunes, cerebral microbleeds and enlarged perivascular spaces. Researchers from the Rotterdam study recently proposed a MRI-based cSVD Score reflecting the overall burden of cerebrovascular injury (Yilmaz et al., 2018). Here, we explored the relevance of this cSVD Score in distinguishing CADASIL subjects from non-carriers and its relationships to cognition. We evaluated 26 NOTCH3 mutation carriers and 25 non-carriers from large Colombian families. Of the CADASIL subjects, 4 had previous strokes (symptomatic) and 22 had no history of strokes (asymptomatic). All subjects underwent a 3T MRI and a neuropsychological evaluation. Structural MRI markers of cSVD, as well as the cSVD Score, were quantified in each subject following established protocols. Demographic, cognitive and neuroimaging features across groups are presented in Table 1. The cSVD Score significantly differed between groups, after adjusting for age (Figure 1-A). In CADASIL subjects, the cSVD Score was negatively related to performance in Memory, Processing Speed, Executive Function, after accounting for age and education (Figure 1-B). These results suggest that the cSVD Score could be a useful marker of disease severity in CADASIL. Longitudinal studies are now needed to determine if this score allows predicting clinical outcomes in CADASIL, such as stroke or dementia.


2019 ◽  
Vol 20 (3) ◽  
pp. 776 ◽  
Author(s):  
Michael Thrippleton ◽  
Gordon Blair ◽  
Maria Valdes-Hernandez ◽  
Andreas Glatz ◽  
Scott Semple ◽  
...  

A protocol for evaluating ultrasmall superparamagnetic particles of iron oxide (USPIO) uptake and elimination in cerebral small vessel disease patients was developed and piloted. B1-insensitive R1 measurement was evaluated in vitro. Twelve participants with history of minor stroke were scanned at 3-T MRI including structural imaging, and R1 and R2* mapping. Participants were scanned (i) before and (ii) after USPIO (ferumoxytol) infusion, and again at (iii) 24–30 h and (iv) one month. Absolute and blood-normalised changes in R1 and R2* were measured in white matter (WM), deep grey matter (GM), white matter hyperintensity (WMH) and stroke lesion regions. R1 measurements were accurate across a wide range of values. R1 (p < 0.05) and R2* (p < 0.01) mapping detected increases in relaxation rate in all tissues immediately post-USPIO and at 24–30 h. R2* returned to baseline at one month. Blood-normalised R1 and R2* changes post-infusion and at 24–30 h were similar, and were greater in GM versus WM (p < 0.001). Narrower distributions were seen with R2* than for R1 mapping. R1 and R2* changes were correlated at 24–30 h (p < 0.01). MRI relaxometry permits quantitative evaluation of USPIO uptake; R2* appears to be more sensitive to USPIO than R1. Our data are explained by intravascular uptake alone, yielding estimates of cerebral blood volume, and did not support parenchymal uptake. Ferumoxytol appears to be eliminated at 1 month. The approach should be valuable in future studies to quantify both blood-pool USPIO and parenchymal uptake associated with inflammatory cells or blood-brain barrier leak.


Neurology ◽  
2020 ◽  
Vol 95 (24) ◽  
pp. e3331-e3343 ◽  
Author(s):  
Maria J. Knol ◽  
Dongwei Lu ◽  
Matthew Traylor ◽  
Hieab H.H. Adams ◽  
José Rafael J. Romero ◽  
...  

ObjectiveTo identify common genetic variants associated with the presence of brain microbleeds (BMBs).MethodsWe performed genome-wide association studies in 11 population-based cohort studies and 3 case–control or case-only stroke cohorts. Genotypes were imputed to the Haplotype Reference Consortium or 1000 Genomes reference panel. BMBs were rated on susceptibility-weighted or T2*-weighted gradient echo MRI sequences, and further classified as lobar or mixed (including strictly deep and infratentorial, possibly with lobar BMB). In a subset, we assessed the effects of APOE ε2 and ε4 alleles on BMB counts. We also related previously identified cerebral small vessel disease variants to BMBs.ResultsBMBs were detected in 3,556 of the 25,862 participants, of which 2,179 were strictly lobar and 1,293 mixed. One locus in the APOE region reached genome-wide significance for its association with BMB (lead single nucleotide polymorphism rs769449; odds ratio [OR]any BMB [95% confidence interval (CI)] 1.33 [1.21–1.45]; p = 2.5 × 10−10). APOE ε4 alleles were associated with strictly lobar (OR [95% CI] 1.34 [1.19–1.50]; p = 1.0 × 10−6) but not with mixed BMB counts (OR [95% CI] 1.04 [0.86–1.25]; p = 0.68). APOE ε2 alleles did not show associations with BMB counts. Variants previously related to deep intracerebral hemorrhage and lacunar stroke, and a risk score of cerebral white matter hyperintensity variants, were associated with BMB.ConclusionsGenetic variants in the APOE region are associated with the presence of BMB, most likely due to the APOE ε4 allele count related to a higher number of strictly lobar BMBs. Genetic predisposition to small vessel disease confers risk of BMB, indicating genetic overlap with other cerebral small vessel disease markers.


2020 ◽  
Vol 12 ◽  
Author(s):  
Zhihua Xu ◽  
Fangfei Li ◽  
Bing Wang ◽  
Dengxiang Xing ◽  
Yusong Pei ◽  
...  

ObjectiveTo assess the suitability of deep medullary vein visibility in susceptibility weighted imaging—magnetic resonance imaging studies as a method for the diagnosis and evaluation of cerebral small vessel disease progression.MethodsA total of 92 patients with CSVD were enrolled and baseline clinical and imaging data were reviewed retrospectively. Neuroimaging biomarkers of CSVD including high-grade white matter hyperintensity (HWMH), cerebral microbleed (CMB), enlarged perivascular space (PVS), and lacunar infarct (LI) were identified and CSVD burden was calculated. Cases were grouped accordingly as mild, moderate, or severe. The DMV was divided into six segments according to the regional anatomy. The total DMV score (0–18) was calculated as the sum of the six individual segmental scores, which ranged from 0 to 3, for a semi-quantitative assessment of the DMV based on segmental continuity and visibility.ResultsThe DMV score was independently associated with the presence of HWMH, PVS, and LI (P &lt; 0.05), but not with presence and absence of CMB (P &gt; 0.05). Correlation between the DMV score and the CSVD burden was significant (P &lt; 0.05) [OR 95% C.I., 1.227 (1.096–1.388)].ConclusionThe DMV score was associated with the presence and severity of CSVD.


Stroke ◽  
2019 ◽  
Vol 50 (Suppl_1) ◽  
Author(s):  
Chia-Ling Phuah ◽  
Yasheng Chen ◽  
Ziyang Liu ◽  
Nirupama Yechoor ◽  
Helen Hwang ◽  
...  

2015 ◽  
Vol 36 (1) ◽  
pp. 228-240 ◽  
Author(s):  
Philip Benjamin ◽  
Eva Zeestraten ◽  
Christian Lambert ◽  
Irina Chis Ster ◽  
Owen A Williams ◽  
...  

Detecting treatment efficacy using cognitive change in trials of cerebral small vessel disease (SVD) has been challenging, making the use of surrogate markers such as magnetic resonance imaging (MRI) attractive. We determined the sensitivity of MRI to change in SVD and used this information to calculate sample size estimates for a clinical trial. Data from the prospective SCANS (St George’s Cognition and Neuroimaging in Stroke) study of patients with symptomatic lacunar stroke and confluent leukoaraiosis was used ( n = 121). Ninety-nine subjects returned at one or more time points. Multimodal MRI and neuropsychologic testing was performed annually over 3 years. We evaluated the change in brain volume, T2 white matter hyperintensity (WMH) volume, lacunes, and white matter damage on diffusion tensor imaging (DTI). Over 3 years, change was detectable in all MRI markers but not in cognitive measures. WMH volume and DTI parameters were most sensitive to change and therefore had the smallest sample size estimates. MRI markers, particularly WMH volume and DTI parameters, are more sensitive to SVD progression over short time periods than cognition. These markers could significantly reduce the size of trials to screen treatments for efficacy in SVD, although further validation from longitudinal and intervention studies is required.


2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Daqiang Ke ◽  
Feng Zhou ◽  
Hui Liang ◽  
Yang Xu ◽  
Haiyan Lou

Intracranial hemorrhage or microbleeds and leukoaraiosis have an overlap in biology. Hyperlipidemia may reduce the risk of ICH or cerebral microbleeds; studies focusing on the relationship between different lipid profiles and severity of periventricular hyperintensities (PVH) and subcortical white matter lesions (SWMLs) in the cerebral small vessel disease are limited. Methods. Patients with recent first lacunar infarct were recruited. PVH and SWMLs were accessed on MRI with the Fazekas scale, and lipid levels were measured. Univariate and multivariable regression analyses were used to assess the relation between different lipid profiles and severity of PVH and SWMLs. Results. In univariate analyses, advancing age was correlated with increasing severity of leukoaraiosis (P<0.001). There was an inverse relationship between hypertriglyceridemia (hyper-TG) (≥1.7 mmol/l) and severity of leukoaraiosis (P<0.05). In the multivariable analysis, after controlling for age, sex, and significant risk factors in the univariate and age-adjusted analyses, hyper-TG demonstrated a protective effect on the severity of PVH and SWMLs (P<0.05). Higher total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were not associated with leukoaraiosis. Conclusions. Hyper-TG is associated with the severity of leukoaraiosis independent of other risk factors, and it might be a protective role in cerebral small vessel disease.


2021 ◽  
Vol 12 ◽  
Author(s):  
Nicholas R. Evans ◽  
Jason M. Tarkin ◽  
Jessica Walsh ◽  
Mohammed M. Chowdhury ◽  
Andrew J. Patterson ◽  
...  

Background: Atherosclerosis is a systemic inflammatory disease, with common inflammatory processes implicated in both atheroma vulnerability and blood-brain barrier disruption. This prospective multimodal imaging study aimed to measure directly the association between systemic atheroma inflammation (“atheroinflammation”) and downstream chronic cerebral small vessel disease severity.Methods: Twenty-six individuals with ischemic stroke with ipsilateral carotid artery stenosis of &gt;50% underwent 18fluoride-fluorodeoxyglucose-positron emission tomography within 2 weeks of stroke. Small vessel disease severity and white matter hyperintensity volume were assessed using 3-tesla magnetic resonance imaging also within 2 weeks of stroke.Results: Fluorodeoxyglucose uptake was independently associated with more severe small vessel disease (odds ratio 6.18, 95% confidence interval 2.1–18.2, P &lt; 0.01 for the non-culprit carotid artery) and larger white matter hyperintensity volumes (coefficient = 14.33 mL, P &lt; 0.01 for the non-culprit carotid artery).Conclusion: These proof-of-concept results have important implications for our understanding of the neurovascular interface and potential therapeutic exploitation in the management of systemic atherosclerosis, particularly non-stenotic disease previously considered asymptomatic, in order to reduce the burden of chronic cerebrovascular disease.


2021 ◽  
Vol 13 ◽  
Author(s):  
Wenbo Sun ◽  
Yufan Luo ◽  
Shufan Zhang ◽  
Wenmei Lu ◽  
Luqiong Liu ◽  
...  

Objectives: This study aimed to investigate the association between plasma von Willebrand factor (VWF) level, ADAMTS13 activity, and neuroimaging features of cerebral small vessel disease (CSVD), including the CSVD neuroimaging markers and the overall CSVD burden.Methods: CSVD patients admitted to our hospital from 2016 to 2020 were recruited. Plasma VWF level and ADAMTS13 activity were measured. The overall effect of CSVD on the brain was described as a validated CSVD score. We evaluated the association between VWF levels, ADAMTS13 activity, and the increasing severity of CSVD score by the logistic regression model.Results: We enrolled 296 patients into this study. The mean age of the sample was 69.0 years (SD 7.0). The mean VWF level was 1.31 IU/mL, and the ADAMTS13 activity was 88.01 (SD 10.57). In multivariate regression analysis, lower ADAMTS13 activity and higher VWF level was related to white matter hyperintensity (WMH) [β = −7.31; 95% confidence interval (CI) (−9.40, −4.93); p&lt;0.01; β = 0.17; 95% confidence interval (0.11, 0.23); p&lt;0.01], subcortical infarction (SI) [(β = −9.22; 95% CI (−11.37, −7.06); p&lt;0.01); β = 0.21; 95% confidence interval (0.15, 0.27); p&lt;0.01] independently, but not cerebral microbleed (CMB) [(β = −2.3; 95% CI (−4.95, 0.05); p = 0.22); β = 0.02; 95% confidence interval (−0.05, 0.08); p = 0.63]. Furthermore, ADAMTS13 activity was independently negatively correlated with the overall CSVD burden (odd ratio = 21.33; 95% CI (17.46, 54.60); p &lt; 0.01) after adjustment for age, history of hypertension, and current smoking.Conclusions: Reducing ADAMTS13 activity change is related to white matter hyperintensity, subcortical infarction, but not with cerebral microhemorrhage. In addition, ADAMTS13 may have played an essential role in the progression of CSVD.


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